The first water soluble, bisphosphonate (BP, not bisphosphonic acid)-functionalized poly(amido amine) macromer (PAA-BP) is synthesized and used as a crosslinker for synthesis of a biodegradable and biocompatible hydrogel for tissue engineering scaffolds. The synthesis of PAA-BP is performed in three steps, the first two giving the control macromers (PAA-NHBoc and PAA-NH₂): i) Michael addition reaction of N,N’-methylene bisacrylamide and N-Boc-1,6-hexanediamine (acrylamide/amine ratios of 1.2), ii) deprotection of Boc-protected amine groups, iii) Michael addition reaction of the amine groups with tetraethyl vinylidene bisphosphonate. The degree of BP substitution is 50% and molecular weight of the PAA-BP macromer is found to be 4800 g/mol. These macromers are incorporated into hydrogels by copolymerization with 2-hydroxyethyl methacrylate and the influence of bisphosphonate functionality on hydrogel properties; degradation, swelling, mechanical and mineralization, is investigated. The mineralization abilities, hence the mechanical properties of the hydrogels are strongly influenced by the BP functionality; PAA-BP forming strong (E = 83 ± 1 kPa) hydrogel-apatite composites, PAA-NH₂ also working to a lesser degree (E = 54 ± 3 kPa). Cytocompatibility of the hydrogels is observed on Saos-2 human osteosarcoma, U-2 OS human bone osteosarcoma epithelial, C2C12 mouse myoblast muscle and NIH mouse embryonic fibroblast 3T3 cells. PAA-BP crosslinked hydrogels facilitate adhesion of C2C12 cells after mineralization. In summary, BP-functionalized hydrogel may have a potential impact on bone tissue engineering.

第一个水溶性双膦酸盐（BP，不是双膦酸）官能化聚（酰胺胺）大分子单体（PAA-BP）被合成并用作交联剂，用于合成用于组织工程支架的可生物降解和生物相容性水凝胶。PAA-BP 的合成分三步进行，前两步给出对照大分子单体（PAA-NHBoc 和 PAA-NH ₂）：i) N,N'-亚甲基双丙烯酰胺和N 的迈克尔加成反应-Boc-1,6-己二胺（丙烯酰胺/胺比为1.2），ii）Boc保护的胺基团的脱保护，iii）胺基团与四乙基亚乙烯基双膦酸酯的迈克尔加成反应。BP 取代度为 50%，PAA-BP 大分子单体的分子量为 4800 g/mol。这些大分子单体通过与甲基丙烯酸 2-羟乙酯的共聚以及双膦酸酯官能团对水凝胶性能的影响而结合到水凝胶中；降解、膨胀、机械和矿化，进行了研究。矿化能力，因此水凝胶的机械性能受 BP 功能的强烈影响；PAA-BP 形成强 (E = 83 ± 1 kPa) 水凝胶-磷灰石复合材料，PAA-NH ₂也可以在较小程度上工作（E = 54 ± 3 kPa）。在 Saos-2 人骨肉瘤、U-2 OS 人骨骨肉瘤上皮细胞、C2C12 小鼠成肌细胞和 NIH 小鼠胚胎成纤维细胞 3T3 细胞上观察到水凝胶的细胞相容性。PAA-BP 交联水凝胶促进矿化后 C2C12 细胞的粘附。总之，BP 功能化水凝胶可能对骨组织工程产生潜在影响。